The present invention is related to compositions and methods containing Se-methyl-L-selenocysteine, and the use of these compositions to provide health benefits in animals and humans.
The parent application disclosed novel processes for preparing Se-alkylselenocysteine, Se-allylselenocysteine, Se-arylselenocysteine. The current invention provides compositions containing Se-methyl-L-selenocysteine with enhanced bioavailability, for nutritional supplementation and pharmaceutical use in humans and animals. The bioavailability is enhanced by the addition of black pepper extract (standardized to contain 95–98% piperine).
Selenium is a vital trace element nutrient with multiple roles in the growth and functioning of living cells in higher animals and humans. At the molecular level, selenium (as selenocysteine) is an essential component of the active sites of the antioxidant enzyme glutathione peroxidase, and the enzymes participating in thyroid functions iodothyronine-5′-deiodinase and mammalian thioredoxin reductase. Selenium is also present in several other mammalian selenoproteins. Low selenium status has been linked with the occurrence of decreased immunity to diseases and the prevalence of various forms of cancer.
Selenium occurs in foods, through uptake by plants from the soil, in the form of the selenoamino acids, selenome-thionine and selenocysteine, and their derivatives. However, as the element is unevenly distributed in the earth's crust, dietary supplementation is often needed. Organic selenium compounds are preferred for supplementation on account of their superior bioavailability. An ideal nutritional supplement would be a selenium enriched edible plant part wherein the selenium metabolically accumulates in the form of bioavailable organic selenium compounds. Plants that naturally contain higher levels of the sulfur containing amino acids such as those from the Allium and Brassica species are preferred for enrichment, based on metabolic criteria. Selenium-enriched garlic is reported to be useful as a nutritional supplement in the prevention of cancer (Ip, et al., 1992, 1996; Ip and Lisk, 1993, 1997; Lu et al., 1996).
Clinical intervention trials and in vitro data revealed the efficacy of selenium in the form of selenium yeast or selenomethionine in cancer prevention (Clark et al., 1996, 1998). Ip et al (2000) described the role of chemical speciation on the comparative activity of selenium-enriched garlic and selenium yeast in mammary cancer prevention in rats, wherein selenium-enriched garlic was shown to be more efficacious than selenium yeast. γ-glutamyl Se-methylselenocysteine is reported to be the major form of selenium in selenium-enriched garlic while L-Selenomethionine was shown to be the major form of selenium in selenium enriched yeast.
Laboratory studies indicate that γ-Glutamyl-Se-methyl-L-selenosysteine is an effective chemopreventive agent, serving as a carrier for Se-Methyl-L-selenocysteine (Dong et al., 2001; Medina et al., 2001). Se-Methyl-L-selenocysteine is a well researched chemopreventive organoselenium compound, which is not incorporated in the body proteins, and is therefore less toxic than other forms of supplemental selenium (Ip et al., 1994; Medina et al., 2001).
A study that compared the chemopreventive activities of selenium compounds, in the rat dimethyl-benz(a)anthracene-induced mammary tumor model reported that 1–2 ppm Se in the diet of rats 1 week before dimethylbenz(a)anthracene administration and continuing until sacrifice, resulted in tumor inhibition. The efficacy of the selenium compounds was in the following order: Se-methylselenocysteine greater than selenite greater than selenocysteine greater than dimethyl selenoxide (Ip et al., 1991).
In a bioavailability study using Se-methylselenocysteine, dimethyl selenoxide, and trimethylselenonium as the starting compounds for delivering selenium with one, two, or three methyl groups, researchers measured the ability of these compounds to restore glutathione peroxidase activity in selenium-depleted animals. All three compounds were able to fully replete this enzyme, although with a wide range of efficiency (Se-methylselenocysteine greater than dimethyl selenoxide greater than trimethylselenonium). (Ip et al., 1991).
Spallholz, J. E.; Reid, T. W.; Walkup, R. D. described a method of using synthetic L-Se-methylselenocysteine as a nutraceutical and a method of its synthesis, EP 1 205 471, 2001 and U.S. 20030083383 A1. They claim the health benefits of Se-methyl-L-selenocysteine as a nutritional supplement in humans and animals.
U.S. Pat. Nos. 5,536,506, 5,744,161, 5,972,382, 6,054,585 by Majeed, et al. describe the use of black pepper extract containing 95–98% piperine to enhance the bioavailability of several nutritional compounds and herbal extracts.
The parent application disclosed novel methods for the synthesis of Se-methyl-L-selenocysteine and related compounds. The method of the current invention permits the utilization of lower amounts of Se-methyl-L-selenocysteine in formulations with enhanced efficacy, and lowered risk of selenium toxicity.
The composition also effectively suppresses liver injury indicating superior antioxidant and anti-inflammatory effects. Selenium compounds for example Ebselen are reported to inhibit macrophage induced liver injury (Koyanagi, wt al. 2001).
The composition is also useful in autoimmune disorders such as psoriasis. Selenium nutritional status is reported to be insufficient in patients with long term psoriasis (Harvima, 1993).
The following is a list of literature cited in this application, each of which is hereby incorporated by reference in its entirety:    1. Ip, C., Lisk, D. J, and Stoewsand, G. S. 1992. “Mammary Cancer prevention by Regular Garlic and Selenium-Enriched Garlic.” Nutr. Cancer 17, 279–286.    2. Ip. C, and Lisk, D. J. 1996. “The attributes of Selenium—Enriched Garlic in Cancer Prevention.” In Dietary Phytochemicals in Cancer Prevention and Treatment 15, 179–187.    3. Ip. C, and Lisk, D. J. 1993. “Bioavailability of Selenium From SeleniumEnriched Garlic.” Nutr. Cancer 20, 129–137.    4. Ip, C and Lisk, D. J. 1997. “Modulation of phase I and Phase II Xenobiotic-metabolizing Enzymes by Enriched Garlic in rats.” Nutr. and Cancer 28(2), 184–188.    5. Lu., J., Pei H., Ip C., Lisk D J., Ganther H and Thompson H J., 1996. Effect on an aqueous extract of selenium enriched garlic on in vitro and in vivo efficacy in cancer prevention. Carcinogenesis,17(9): 1903 1907.    6. Ip, C; Ganther, H. Novel Strategies In Selenium Cancer Chemoprevention Research; In Selenium In Biology and Human Health; Burk, R. F. Ed; (1994) Springer-Verlag, New York: 169 180.    7. Ip. C., et al. 2000. Chemical Speciation Influences Comparative Activity of Selenium-Enriched Garlic and Yeast in Mammary Cancer Prevention. J. Agric. Food Chem. 48, 2062–2070    8. Dong, Y. et al. 2001 Characterization and Biological Activity of γ-Glutamyl-Se Methylselenocysteine: A Novel, Naturally Occurring Anticancer Agent From Garlic. Cancer Res. 61:2923–2928.    9. Medina, D. et al. 2001 Se-Methylselenocysteine: A new compound for chemoprevention of breast cancer. Nutrition and Cancer 40(1):12–17.    10. Clark L C, et al. 1996 Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA. 276(24):1957–63.    11. Clark, L C et al. 1998 Inhibitory effect of selenomethionine on the growth of three selected human tumor cell lines. Cancer Lett.; 125(1–2):103–10.    12. Ip, C., et al. 1991. Chemical form of selenium, critical metabolites, and cancer prevention. Cancer Res.; 51(2):595–600.    13. Koyanagi, T. et al. 2001 The selenoorganic compound ebselen suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats. Int. J. Mol. Med. 7(3): 321–327.    14. Harvima, R. J. (1993) Screening of effects of selenomethionine-enriched yeast supplementation on various immunological and chemical parameters of skin and blood in psoriatic patients. Acta Derm. Venerol. 73(2): 88–91.